AMG-458Potent c-Met inhibitor CAS# 913376-83-7 |
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Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
| Cas No. | 913376-83-7 | SDF | Download SDF |
| PubChem ID | 24764449 | Appearance | Powder |
| Formula | C30H29N5O5 | M.Wt | 539.58 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble to 21 mg/mL (38.91 mM) in DMSO | ||
| Chemical Name | 1-(2-hydroxy-2-methylpropyl)-N-[5-(7-methoxyquinolin-4-yl)oxypyridin-2-yl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide | ||
| SMILES | CC1=C(C(=O)N(N1CC(C)(C)O)C2=CC=CC=C2)C(=O)NC3=NC=C(C=C3)OC4=C5C=CC(=CC5=NC=C4)OC | ||
| Standard InChIKey | GLBZSOQDAOLMGC-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C30H29N5O5/c1-19-27(29(37)35(20-8-6-5-7-9-20)34(19)18-30(2,3)38)28(36)33-26-13-11-22(17-32-26)40-25-14-15-31-24-16-21(39-4)10-12-23(24)25/h5-17,38H,18H2,1-4H3,(H,32,33,36) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | AMG 458 is a potent inhibitor of c-Met with a Ki value of 1.2 nM. | ||||||
| Targets | c-Met (H1094R) | c-Met (V1092I) | c-Met (Human) | c-Met (Mouse) | c-Met (D1228H) | ||
| IC50 | 0.5 nM(Ki) | 1.1 nM(Ki) | 1.2 nM(Ki) | 2.0 nM(Ki) | 2.2 nM(Ki) | ||
AMG-458 Dilution Calculator
AMG-458 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.8533 mL | 9.2665 mL | 18.5329 mL | 37.0659 mL | 46.3323 mL |
| 5 mM | 0.3707 mL | 1.8533 mL | 3.7066 mL | 7.4132 mL | 9.2665 mL |
| 10 mM | 0.1853 mL | 0.9266 mL | 1.8533 mL | 3.7066 mL | 4.6332 mL |
| 50 mM | 0.0371 mL | 0.1853 mL | 0.3707 mL | 0.7413 mL | 0.9266 mL |
| 100 mM | 0.0185 mL | 0.0927 mL | 0.1853 mL | 0.3707 mL | 0.4633 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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AMG-458 is a potent and selective inhibitor of human and mouse c-Met with IC50 value of 1.2 nM and 2.0 nM respectively.
c-Met, also known as hepatocyte growth factor receptor, is a receptor tyrosine kinase that can be activated by hepatocyte growth factor/scatter factor (HGF/SF). It is a membrane protein which plays an essential role in embryonic development and wound healing.
Recent study investigated the effect of AMG-456 treatment on cell radiosensitizing response. The results showed that AMG-458 treatment enhanced radiosensitivity in H441 with higher levels of c-Met but not in A549 with lower expression of c-Met [1].
This component was also used in an animal model to study the role of c-Met in the development of tumor. For instance, orally administration of AMG-456 resulted in significant inhibition of tumor growth in /TPR-Met and U-87 MG xenograft models without any adverse effect on body weight [2].
References:
1. Li B, Torossian A, Sun Y, Du R, Dicker AP, Lu B. Higher levels of c-Met expression and phosphorylation identify cell lines with increased sensitivity to AMG-458, a novel selective c-Met inhibitor with radiosensitizing effects. Int J Radiat Oncol Biol Phys 2012,84:e525-531.
2. Liu L, Siegmund A, Xi N, Kaplan-Lefko P, Rex K, Chen A, et al. Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-meth yl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J Med Chem 2008,51:3688-3691.
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Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-meth yl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458).[Pubmed:18553959]
J Med Chem. 2008 Jul 10;51(13):3688-91.
Deregulation of the receptor tyrosine kinase c-Met has been implicated in human cancers. Pyrazolones with N-1 bearing a pendent hydroxyalkyl side chain showed selective inhibition of c-Met over VEGFR2. However, studies revealed the generation of active, nonselective metabolites. Blocking this metabolic hot spot led to the discovery of 17 (AMG 458). When dosed orally, 17 significantly inhibited tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight.
Higher levels of c-Met expression and phosphorylation identify cell lines with increased sensitivity to AMG-458, a novel selective c-Met inhibitor with radiosensitizing effects.[Pubmed:22836051]
Int J Radiat Oncol Biol Phys. 2012 Nov 15;84(4):e525-31.
PURPOSE: c-Met is overexpressed in some non-small cell lung cancer (NSCLC) cell lines and tissues. Cell lines with higher levels of c-Met expression and phosphorylation depend on this receptor for survival. We studied the effects of AMG-458 on 2 NSCLC cell lines. METHODS AND MATERIALS: 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr azolium assays assessed the sensitivities of the cells to AMG-458. Clonogenic survival assays illustrated the radiosensitizing effects of AMG-458. Western blot for cleaved caspase 3 measured apoptosis. Immunoblotting for c-Met, phospho-Met (p-Met), Akt/p-Akt, and Erk/p-Erk was performed to observe downstream signaling. RESULTS: AMG-458 enhanced radiosensitivity in H441 but not in A549. H441 showed constitutive phosphorylation of c-Met. A549 expressed low levels of c-Met, which were phosphorylated only in the presence of exogenous hepatocyte growth factor. The combination of radiation therapy and AMG-458 treatment was found to synergistically increase apoptosis in the H441 cell line but not in A549. Radiation therapy, AMG-458, and combination treatment were found to reduce p-Akt and p-Erk levels in H441 but not in A549. H441 became less sensitive to AMG-458 after small interfering RNA knockdown of c-Met; there was no change in A549. After overexpression of c-Met, A549 became more sensitive, while H441 became less sensitive to AMG-458. CONCLUSIONS: AMG-458 was more effective in cells that expressed higher levels of c-Met/p-Met, suggesting that higher levels of c-Met and p-Met in NSCLC tissue may classify a subset of tumors that are more sensitive to molecular therapies against this receptor.
